Article
Endocrinology & Metabolism
Sarah M. Gray, Andrew L. Hoselton, Radha Krishna, Cris A. Slentz, David A. D'Alessio
Summary: GLP-1r signaling contributes to insulin secretion during alpha-cell activation, independent of increased circulating GLP-1, and may be affected by DPP4 inhibition.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Bo Ahren
Summary: In this study, the contribution of GIP and GLP-1 to insulin response to oral glucose in female mice was investigated using receptor antagonists. It was found that both GIP and GLP-1 are required for a normal incretin effect in female mice, and no other incretin hormone is likely present in this species.
Review
Medicine, General & Internal
Julia Ast, Johannes Broichhagen, David J. Hodson
Summary: GLP1R and GIPR are important targets for diabetes and obesity treatment, but little is known about their localization and detection. The low abundance of GLP1R and GIPR, along with a lack of specific reagents, complicates the understanding of their mechanisms of action in target organs.
Review
Endocrinology & Metabolism
Michael A. Nauck, Daniel R. Quast, Jakob Wefers, Andreas F. H. Pfeiffer
Summary: Incretin hormones GIP and GLP-1 play a significant role in insulin secretion and glucose tolerance in the gut-endocrine pancreas axis. They also have additional effects on bone remodelling, lipid storage, gastric emptying, and may provide benefits for cardiovascular complications and neurodegenerative disorders. Recent research on GIP/GLP-1 receptor co-agonists has renewed interest in the potential therapeutic applications of incretin hormones.
DIABETES OBESITY & METABOLISM
(2021)
Review
Immunology
Jie Huang, Xinxin Liu, Yingying Wei, Xinlu Li, Shupei Gao, Lingli Dong, Xiaoquan Rao, Jixin Zhong
Summary: DPP4 is a widely expressed protease that alters the bioactivity of its substrates by cleaving off dipeptides from their N-terminus. In addition to its enzymatic functions, DPP4 is involved in various cellular processes and plays a crucial role in immune regulation and autoimmune rheumatic diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Endocrinology & Metabolism
Melinda Danowitz, Diva D. De Leon
Summary: Incretin hormones, especially GLP-1, play an important role in the pathophysiology of hyperinsulinemic hypoglycemia. Understanding the mechanisms of incretin hormones is crucial for exploring GLP-1 receptor as a therapeutic target for these conditions.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Endocrinology & Metabolism
Qiming Tan, Seun E. Akindehin, Camila E. Orsso, Richelle C. Waldner, Richard D. DiMarchi, Timo D. Mueller, Andrea M. Haqq
Summary: GLP-1 has been extensively studied as a therapeutic target for obesity and type 2 diabetes. Improvement in the pharmacokinetic profile of GLP-1R agonists and the recent clinical success of GIPR agonists have opened up new possibilities for the treatment of obesity and diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Pharmacology & Pharmacy
Katherine O. Kopp, Elliot J. Glotfelty, Yazhou Li, Nigel H. Greig
Summary: Chronic neuroinflammation is a key feature of neurodegenerative diseases, and targeting this inflammation has not been effectively utilized in clinical treatments. The risk of inflammation and neurodegenerative diseases is associated with type 2 diabetes and insulin resistance, suggesting that alleviating diabetes pathology may help treat neuroinflammation and neurodegeneration. GLP-1 is a hormone that promotes healthy insulin signaling and has shown anti-inflammatory, neurotrophic, and neuroprotective properties in preclinical neurodegenerative disease models.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Immunology
Shabnam Radbakhsh, Stephen L. Atkin, Luis E. Simental-Mendia, Amirhossein Sahebkar
Summary: Incretin hormones, such as GLP, GIP, and GLP-2, have immunomodulatory effects on the immune system by regulating T and B cell activation. This review explores the potential benefits of incretin-based therapy for treating autoimmune diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Medicine, Research & Experimental
Akira Mima, Atsuo Nomura, Takeshi Fujii
Summary: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and is considered one of the most significant complications of diabetes. Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, have shown potential in reducing DKD. While GIP has been considered unsuitable for type 2 diabetes treatment in the past, recent studies have demonstrated its possible efficacy with improved glycemic control. Novel dual- or triple-receptor agonists that target GLP-1, GIP, and glucagon receptors are being developed to address multiple metabolic pathways in type 2 diabetes.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Endocrinology & Metabolism
Jonathan M. Wilson, Yanzhu Lin, M. Jane Luo, Gary Considine, Amy L. Cox, Lenden M. Bowsman, Deborah A. Robins, Axel Haupt, Kevin L. Duffin, Giacomo Ruotolo
Summary: In a phase 2 trial, tirzepatide reduced HbA1c and body weight dose-dependently in patients with type 2 diabetes, and also decreased several biomarkers associated with cardiovascular risk factors, showing potential positive effects on cardiovascular health.
DIABETES OBESITY & METABOLISM
(2022)
Article
Chemistry, Medicinal
Jeisson D. Corredor, Camilo Febres-Molina, Gonzalo A. Jana, Veronica A. Jimenez
Summary: In this study, molecular dynamics simulations were used to reveal a novel water-mediated mechanism for the covalent inhibition of dipeptidyl peptidase-4 (DPP4) by Vildagliptin (VIL). The findings have important implications for understanding the molecular features of DPP4 inhibition by VIL and for the development of new derivatives with improved structural or mechanistic profiles.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Multidisciplinary Sciences
Andrew R. Castle, Sang-Gyun Kang, Ghazaleh Eskandari-Sedighi, Serene Wohlgemuth, My-Anh Nguyen, Daniel J. Drucker, Erin E. Mulvihill, David Westaway
Summary: In prion infections, the cellular prion protein (PrPC) can convert to pathogenic conformations (PrPSc) and bind toxic oligomers formed by amyloid-beta alpha-synuclein and tau. β-Endoproteolysis of PrPC into N- and C-terminal fragments (N2 and C2) is of interest, but the proteolytic mechanism remains unconfirmed. A recent study identified S9B peptidase subfamily membrane proteins as potential β-cleavage candidates for PrPC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Endocrinology & Metabolism
Baptist Gallwitz
Summary: Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists, have been established in the treatment of type 2 diabetes. The development of novel dual- or triple-receptor agonists aims to target multiple metabolic pathways simultaneously. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown promising effects in reducing glycemic parameters and body weight. This article provides an overview of the current clinical study program and highlights the potential indications for tirzepatide in the treatment of obesity and comorbidities of type 2 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pharmacology & Pharmacy
Neil Tanday, Peter R. Flatt, Nigel Irwin
Summary: GLP-1, as an important incretin hormone, has made significant progress in drug development and clinical application, offering a wide range of metabolic benefits. With the clinical approval and continuous evolution of GLP-1 receptor ligands, it is expected that GLP-1 has great potential in treating diseases beyond diabetes and obesity.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Nutrition & Dietetics
Thirza van Deuren, Lotte Smolders, Anita Hartog, Freek G. G. Bouwman, Jens J. J. Holst, Koen Venema, Ellen E. E. Blaak, Emanuel E. E. Canfora
Summary: This study compared the bioaccessibility of two different SCFA-enriched triglycerides and investigated the effects of orally administered Akovita SCT on postprandial metabolism in men with overweight/obesity. The results showed that Akovita SCT delayed the release of SCFA and increased circulating butyrate and hexanoate levels without affecting metabolic parameters.
FRONTIERS IN NUTRITION
(2023)
Article
Pharmacology & Pharmacy
R. L. Nielsen, O. Bornaes, I. K. Storgaard, T. Kallemose, L. M. Jorgensen, B. N. Jawad, I. Altintas, H. G. Juul-Larsen, J. Tavenier, J. A. Durhuus, A. K. P. Bengaard, J. J. Holst, M. Kolko, D. P. Sonne, T. Breindahl, M. Damgaard, E. Porrini, M. Hornum, O. Andersen, M. M. Pedersen, H. H. Rasmussen, T. Munk, T. M. Lund, P. S. Jensen, A. L. Andersen, M. B. Houlind
Summary: This study aims to investigate the appetite-stimulating effects of cannabis-based medicine in older patients and compare the accuracy of different estimated glomerular filtration rate (eGFR) equations. The study consists of two substudies, including a double-blinded, randomized, placebo-controlled trial and a single-dose pharmacokinetics study. The primary endpoints are differences in energy intake and the accuracy of eGFR equations. Secondary endpoints include safety parameters, changes in appetite hormones, and the creation of pharmacokinetic models.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Medicine, Research & Experimental
Sarina Gadgaard, Johanne A. Windelov, Sine P. Schiellerup, Jens J. Holst, Bolette Hartmann, Mette M. Rosenkilde
Summary: In this study, lipidated GLP-2R agonists were created and tested for their effects on the intestine and bone. The variants with lipidations at positions 12, 16, and 20 showed improved potency and efficacy compared to native GLP-2.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Endocrinology & Metabolism
Niels B. Dalsgaard, Laerke S. Gasbjerg, Mads M. Helsted, Laura S. Hansen, Nina L. Hansen, Kirsa Skov-Jeppesen, Bolette Hartmann, Jens J. Holst, Tina Vilsboll, Filip K. Knop
Summary: In patients with type 2 diabetes, treatment with acarbose reduces the postprandial suppression of bone resorption, possibly due to increased secretion of the gut hormone GLP-1. The impairment of bone resorption suppression caused by acarbose may be partially reversed by GLP-1 receptor antagonism. Additionally, acarbose-induced reductions in other factors, such as glucose-dependent insulinotropic polypeptide, may also contribute to this phenomenon.
Article
Cardiac & Cardiovascular Systems
Rasmus M. Sandsdal, Christian R. Juhl, Simon B. K. Jensen, Julie R. Lundgren, Charlotte Janus, Martin B. Blond, Mads Rosenkilde, Adrian F. Bogh, Lasse Gliemann, B. Jensen Jens-Erik, Charalambos Antoniades, Bente M. Stallknecht, Jens J. Holst, Sten Madsbad, Signe S. Torekov
Summary: This study investigated the effects of exercise, a GLP-1 RA, or the combination on metabolic syndrome severity, abdominal obesity, and inflammation. The findings suggest that exercise, liraglutide treatment, or the combination can reduce the risk of cardiovascular disease and type 2 diabetes, as well as decrease the severity of metabolic syndrome, abdominal obesity, and inflammation.
CARDIOVASCULAR DIABETOLOGY
(2023)
Article
Medicine, General & Internal
Juan P. Frias, Srikanth Deenadayalan, Lars Erichsen, Filip K. Knop, Ildiko Lingvay, Stanislava Macura, Chantal Mathieu, Sue Pedersen, Melanie Davies
Summary: This study assessed the efficacy and safety of co-administered semaglutide with cagrilintide in participants with type 2 diabetes. The results showed that the combination treatment resulted in clinically relevant improvements in glycemic control and weight loss compared to cagrilintide alone, and it was well tolerated.
Review
Endocrinology & Metabolism
Sofie Haedersdal, Andreas Andersen, Filip K. K. Knop, Tina Vilsboll
Summary: Insulin and glucagon have opposing effects on glucose metabolism, with the pancreatic islet beta-cells and alpha-cells acting as functional antagonists. The understanding of glucagon secretion has shifted towards the importance of alpha-cell-beta-cell crosstalk and the local paracrine actions on glucagon. Dysregulated glucagon secretion plays a role in metabolic diseases such as obesity, non-alcoholic fatty liver disease, and type 2 diabetes mellitus, and targeting glucagon holds clinical potential.
NATURE REVIEWS ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Michael M. Richter, Maria S. Svane, Viggo B. Kristiansen, Jens J. Holst, Sten Madsbad, Kirstine N. Bojsen-Moller
Summary: Follistatin is secreted from the liver and plays a role in muscle growth and insulin sensitivity. Protein intake stimulates the secretion of follistatin, possibly through increased glucagon levels when insulin concentrations are low. The study investigated the levels of circulating follistatin after meals in patients who had undergone bariatric surgery, and found that follistatin secretion was accelerated in patients after RYGB surgery, which may be due to increased protein absorption rate rather than changes in the glucagon-to-insulin ratio.
Article
Biochemistry & Molecular Biology
Sasha A. S. Kjeldsen, Michael M. Richter, Nicole J. Jensen, Malin S. D. Nilsson, Niklas Heinz, Janus D. Nybing, Frederik H. Linden, Erik Hogh-Schmidt, Mikael P. Boesen, Sten Madsbad, Hendrik Vilstrup, Frank Vinholt Schiodt, Andreas Moller, Kirsten N. orgaard, Signe Schmidt, Elias B. Rashu, Lise L. Gluud, Steen B. Haugaard, Jens J. Holst, Jorgen Rungby, Nicolai J. Wewer Albrechtsen
Summary: The study developed an experimental test to evaluate glucagon sensitivity and its impact on amino acid and glucose metabolism in humans. The test was based on nine pilot studies and calculated a glucagon sensitivity index. Additionally, a comprehensive study protocol was described to apply the glucagon sensitivity test in a cross-sectional study. This research provides valuable insights into the physiological and pathophysiological mechanisms of glucagon action and glucagon-based therapies.
Article
Biochemistry & Molecular Biology
Jens Juul Holst
Summary: Glucagon was discovered as a contaminant of early insulin preparations in 1923 and its hormonal nature was established in the 1950s with the development of radioimmunoassay. Its role in hepatic glucose production and diabetic hyperglycemia has been recognized, but there are still unresolved issues regarding the measurement of glucagon and its extrapancreatic sources.
Article
Medicine, General & Internal
Vanita R. Aroda, Jens Aberle, Lars Bardtrum, Erik Christiansen, Filip K. Knop, Sanaz Gabery, Sue Pedersen, John B. Buse
Summary: This study investigated the efficacy of oral semaglutide at higher doses in patients with inadequately controlled type 2 diabetes and found that the doses of 25 mg and 50 mg were superior to the approved dose of 14 mg in reducing HbA1c and bodyweight. No new safety concerns were identified in the study.
Article
Biochemistry & Molecular Biology
August Pilegaard Prahm, Mark Krogh Hvistendahl, Christopher Filtenborg Brandt, Paul Blanche, Bolette Hartmann, Jens Juul Holst, Palle Bekker Jeppesen
Summary: This study compared the effects of three iso-energetic meals with different macronutrient compositions on postprandial secretion of GLP-2, PYY, and GIP. The results showed that a high protein meal had the highest stimulatory effect on GLP-2 and PYY secretion, while a high carbohydrate meal was most effective for GIP.
Article
Endocrinology & Metabolism
Sondre Meling, Erling Tjora, Heike Eichele, Rasmus B. Nedergaard, Filip K. Knop, Niels Ejskjaer, Siri Carlsen, Pal R. Njolstad, Christina Brock, Eirik Softeland
Summary: This study investigated the association between the incretin effect and autonomic neuropathy in type 2 diabetes patients. It found that rectal hyposensitivity was present in both longstanding and early diabetes, and was associated with gastrointestinal-mediated glucose disposal (GIGD) but not the incretin effect. Both the incretin effect and GIGD were correlated with the degree of dysglycemia and the duration of diabetes.
ENDOCRINOLOGY DIABETES & METABOLISM
(2023)
Article
Gastroenterology & Hepatology
Nina Lon, Sara Engel, Anders Damholt, Brynjulf Mortensen, Anne B. Haaber, Anja Wellejus, Filip K. Knop
Summary: Oral administration of the bacterial strain Bifidobacterium breve Bif195 can reduce the risk of aspirin-induced gastric mucosal damage. This study suggests that Bif195 may serve as a safe supplement during multiple-dosing aspirin treatment.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Endocrinology & Metabolism
Julio Rosenstock, Bertrand Cariou, Johanna Eliasson, Guillaume Frappin, Margit S. Kaltoft, Eduard Montanya, Filip K. Knop
Summary: The aim of this study was to assess the duration and likelihood of achieving HbA1c less than 7.0% in participants with type 2 diabetes using oral semaglutide compared to other medications.
DIABETES OBESITY & METABOLISM
(2023)